Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo

  • Alexandra Schäfer
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 1
  • Frauke Muecksch
    Laboratory of Retrovirology, The Rockefeller University, New York, NY 2
  • Julio C.C. Lorenzi
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 3
  • Sarah R. Leist
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 1
  • Melissa Cipolla
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 3
  • Stylianos Bournazos
    Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 4
  • Fabian Schmidt
    Laboratory of Retrovirology, The Rockefeller University, New York, NY 2
  • Rachel M. Maison
    Laboratory of Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO 8
  • Anna Gazumyan
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 3
  • David R. Martinez
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 1
  • Ralph S. Baric
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 1
  • Davide F. Robbiani
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 3
  • Theodora Hatziioannou
    Laboratory of Retrovirology, The Rockefeller University, New York, NY 2
  • Jeffrey V. Ravetch
    Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY 4
  • Paul D. Bieniasz
    Laboratory of Retrovirology, The Rockefeller University, New York, NY 2
  • Richard A. Bowen
    Laboratory of Animal Reproduction and Biotechnology, Colorado State University, Fort Collins, CO 8
  • Michel C. Nussenzweig
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 3
  • Timothy P. Sheahan
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 1

説明

<jats:p>SARS-CoV-2, the causative agent of COVID-19, has been responsible for over 42 million infections and 1 million deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here, we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a Syrian hamster model of SARS-CoV-2 and in a mouse-adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). Antibody combinations were effective for prevention and in therapy when administered early. However, in vitro antibody neutralization potency did not uniformly correlate with in vivo protection, and some hu-mAbs were more protective in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors contributes to optimal protection against SARS-CoV-2 MA. The data indicate that intact effector function can affect hu-mAb protective activity and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.</jats:p>

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